Gels formed by crosslinking polysaccharides bearing pendant carboxylate groups have been known and used for many years in the areas of dental health care and food preparation technologies. Of these gels, the most commonly encountered are composed of water-insoluble alginates which include, with the exception of magnesium, the alkaline earth metal salts and the group III metal salts of alginic acid. These water-insoluble alginate gels are typically formed by the chemical conversion of water-soluble alginates, in an aqueous solution, into water-insoluble alginates. This conversion usually is accomplished by the reaction of a water-soluble alginate with polyvalent cations released from a soluble di- or trivalent metal salt. The water-soluble alginates include the ammonium, magnesium, potassium, sodium, and other alkali metal salts of alginic acid.
The most common of the alginate gels is composed of calcium alginate. Sources for the crosslinking calcium ions used in the formation of these gels generally include calcium carbonate, calcium sulfate, calcium chloride, calcium phosphate, and calcium tartrate.
Controlling the time of gelation has traditionally been an integral part of conventional methods of preparing these calcium alginate gels and is usually accomplished by regulating the concentration of free calcium ions in the solution. Typically the concentration of free calcium ions is controlled by manipulation of the ionization rate of the calcium salt and/or by the inclusion of other compounds in the solution which react with the free calcium ions.
Conventional processes regulate the rate of ionization by selecting a calcium salt having the desired solubility and/or by adjusting the pH of the solution to increase the solubility of the calcium salt. The solubility of slightly soluble or water-insoluble calcium salts can be increased by lowering the pH of the solution. Generally the pH is lowered by the addition of an acid or by the addition of a substance such as an acid lactone that hydrolyzes to an acid. Commonly used pH adjusters include glucono-delta-lactone and acids such as acetic, adipic, citric, fumaric, lactic and tartaric acid.
The availability of calcium ions can also be controlled by the addition of gel retarders. Known gel retarders are salts having an anion that forms a water-insoluble or slightly water-soluble bond to the calcium ions. The retarder competes with the water-soluble alginate for the free calcium ions thereby depriving the alginate of some of the crosslinking ions and delaying gelation. Common retarders are the alkali metal phosphates, oxalates, and citrates.
Conventional methods for preparing these water-insoluble calcium alginate gels typically involve adding solid water-soluble alginate and solid calcium salt to an aqueous medium as disclosed in U.S. Pat. No. 3,455,701, and U.K. Patent Specification No. 1,579,324, published Nov. 19, 1980, or adding a solution or dispersion of calcium salt to an aqueous solution of water-soluble alginate as disclosed in U.S. Pat. No(s). 2,756,874, 4,381,947 and 4,401,456. Typically these methods include the addition of gel retarders and/or pH adjusters to provide control over the rate of gelation.
Traditionally, water-insoluble alginate gels have been used extensively in dental impression materials and as thickening or setting agents in food preparations. Recently, however, water-insoluble alginate gels have found utility as a form-in-place wound dressing material as disclosed in Swedish Patent Application Publication No. 424,956, published Aug. 23, 1982, and Applicant's copending U.S. patent application entitled "Alginate Hydrogel Foam Wound Dressing".
This newly discovered use for these gels brings with it new concerns with regard to the purity and sterility of the alginate gel being formed. For example, it is generally desirable that retarders and suspending agents which leave residual deposits in the alginate gel network not be present in the gel-forming components used to form alginate gel wound dressing materials. Furthermore, to be effective in preventing the contamination and infection of wounds it is generally desirable that the alginate gel wound dressing material be sterile prior to its application to the wound.
Theoretically, a sterile form-in-place alginate gel wound dressing may be prepared by either (1) sterilizing the gel-forming components separately prior to mixing and maintaining the components in a sterile environment before, during and after mixing until the composite material is applied to the wound, or (2) mixing the gel-forming components together first and then sterilizing the composite material immediately to application to the wound. The latter alternative, however, has little practical utility as it requires each batch of wound dressing material to be individually sterilized prior to its application to the wound, and thereby places unacceptable demands upon the time and facilities of the health care professional preparing the dressing. Likewise, in order for the former alternative to be useful, sterile gel-forming components, and a method of mixing these components while maintaining them in a sterile environment, must be available to the health care professional.
Additionally, it is desirable for the sterile gel-forming components to mix easily and quickly so as to minimize the demands on the health care professional's time and energy required to prepare the wound dressing material. Furthermore, it is desirable for the wound dressing material to gel quickly after application to the wound so as to minimize the inconvenience to the patient.
In light of these concerns, the present invention provides a self-contained gel-forming article useful for preparing sterile water-insoluble alginate gels, and a method for the quick and easy preparation of water-insoluble alginate gels without the use of suspending agents or gel retarders.